The application of spatial transcriptomics to the study of accelerated atherosclerosis in human vein grafts

Qualification: PhD

Department: Cardiovascular Sciences

Application deadline: 4th March 2020

Start date: 28th September 2020

Overview

Supervisors:

Mr Mustafa Zakkar

Professor Gavin Murphy

Dr Marcin Wozniak

Project Details:

There is a unique opportunity to join an established translational research group led by Prof. Gavin Murphy at the BHF-funded Cardiovascular Research Centre in Leicester.

The long saphenous vein (LSV) is the most commonly used conduit in coronary artery bypass graft (CABG) surgery. The LSV however, suffers from the disadvantage of developing late stage vein graft disease (stenosis and occlusion) due to intimal hyperplasia (IH) and accelerated atherosclerosis. Our research group is currently evaluating the cellular and molecular mechanisms underlying these processes using human tissue collected from patients undergoing cardiac surgery. 

To date, there is no successful treatment or prevention strategy for vein graft disease, mainly due to the lack of a comprehensive understanding of the disease's molecular background. That includes changes in the different cell layers of veins in response to a new haemodynamic environment after implantation, interactions between cell types, and genetic phenotypes.

The project involves measuring flows, shear stress and wall tension in human vein grafts in situ. These are then reproduced ex-vivo in segments from the vein used to form the bypass graft. Changes in cell phenotype and cell-cell interaction ex vivo will be compared to the development of neointima measured using optical coherence tomography in the vein grafts in patients at 1 year. 

The PhD studentship will focus on the interaction between acute changes in shear stress in implanted vein grafts and the subsequent personalised changes in cell signalling in the vessel wall. The successful candidate will investigate molecular mechanisms involved in endothelial-to-mesenchymal transition (EndMT) in vein graft samples from patients undergoing CABG.  Expression profiling across three layers of the vein will be performed using cutting-edge spatial sequencing technology. The candidate will also undergo training in MRC key skills including bioinformatics, machine learning, and biostatistics. They will also work as part of an international research group that includes research units in the UK (Oxford and Bristol) and Europe (Milan, Italy).

Funding

Funding

3 Year College of Life Sciences Studentship providing a Stipend at UKRI rates and tuition fee waiver at UK/EU rates.

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject or overseas equivalent. 

The University of Leicester English language requirements apply where applicable.

Informal enquiries

Informal enquiries

For project enquiries please email

Mr Mustafa Zakkar mz207@leicester.ac.uk  or

Dr Marcin Wizniak mw299@leicester.ac.uk.

Enquiries regarding the application process please email pgradmissions@le.ac.uk 

How to apply

How to apply

Please use the Apply button at the bottom of the page and when prompted select September 2020.


Within the application form, please:

Include the project title and the names of the project supervisor in the proposal section

Upload a copy of your CV, a personal statement about why you want to be considered for the project, copies of degree certificates and transcripts, evidence of English proficiency if applicable.

In the funding section state CLS CVS Zakkar 2020 Studentship

Eligibility

Eligibility

UK/EU applicants only please